LURASIDONE IN CHILDREN AND ADOLESCENTS WITH BIPOLAR DEPRESSION ASSOCIATED WITH MIXED (SUBSYNDROMAL HYPOMANIC) FEATURES: POST HOC ANALYSIS OF A RANDOMIZED PLACEBO-CONTROLLED TRIAL

Objectives: The goal of this presentation is to evaluate the efficacy and safety of lurasidone in the treatment of children and adolescents with bipolar disorder presenting with mixed features. Methods: Patients (ages 10-17 years), with a DSM-IV-Text Revision diagnosis of bipolar I disorder, were randomized to six weeks of double-blind treatment with once-daily, flexible dose of lurasidone (20-80 mg) or placebo. The presence of mixed features was defined as a Young Mania Rating Scale (YMRS) score > 5 at study baseline. Efficacy analyses included change from baseline to week six in Children Depression Rating Scale, Revised (CDRS-R) score (the primary outcome) and Clinical Global Impressions, Bipolar Severity of Depression Score (CGI-BP-S), using mixed model for repeated measures analysis. Results: At baseline, mixed features were present in 54.2 percent of patients (lurasidone, n = 97 of 173; placebo, n = 89 of 170). Treatment with lurasidone (vs. placebo) was associated with significantly greater reductions in CDRS-R scores at week six in the mixed-features group (-21.5 vs.-15.9; P < 0.01; effect size = 0.45) and in the group without mixed features (-20.4 vs -14.8; P < 0.01; effect size = 0.45). Likewise, lurasidone was associated with greater effect size (vs. placebo) for reductions in CGI-BP-S scores at week six in the mixed features group (-1.6 vs.-1.1; P < 0.001; effect size = 0.57) and in the group without mixed features (-1.3 vs.-1.0; P = 0.05; effect size = 0.30). Rates of protocol-defined treatment-emergent hypomania or mania were similar for lurasidone and placebo in patients with mixed features (lurasidone 8.2% vs. placebo 9.0%) and without mixed features (lurasidone 1.3% vs. placebo 3.7%). Conclusions: Lurasidone was found in this post hoc analysis to be efficacious in the treatment of child and adolescent patients with bipolar disorder who presented with mixed features (assessed cross-sectionally at study baseline). There was no increased risk of treatment-emergent mania observed in patients with or without mixed features.